The addition of 8-Br-cAMP to primary culture of adrenal chromaffin cells, produces an induction of TH and a two- to three-fold increase in synthesis of enkephalin-like immunoreactive material (ELM). TH and ELM induction is preceded by an activation of cytosol cAPK and by an increase in nuclear protein phosphorylation. The induction of TH, the increase of ELM and the increase of nuclear phosphorylation require that the assembly of microtubular proteins be functional. Anti-microtubular drugs such as colchicine and vinblastine (10-9M) can block the TH and ELM induction elicited by 8-Br-cAMP when the drugs are added less than 15 hours after 8-Br-cAMP. Since colchicine, added with cAMP, also prevents the increase in nuclear phosphorylation, it is possible that the assembly of microtubular proteins might be operative in the intracellular translocation and nuclear uptake of catalytic subunits of cAPK activated by the addition of 8-Br-cAMP. In addition, these data support the view that an increase in nuclear protein phosphorylation is an essential step in the mediating the acceleration of mRNA synthesis and the subsequent increase in TH and ELM synthesis elicited by 8-Br-cAMP.